Hematopoietic stem cell transplantation (HSCT) is the first field where human stem cell therapy was successful. Flooding interest on human stem cell therapy to cure previously incurable diseases is largely indebted to HSCT success. Allogeneic HSCT has been an important modality to cure various diseases including hematologic malignancies, various non-malignant hematologic diseases, primary immunodeficiency diseases, and inborn errors of metabolism, while autologous HSCT is generally performed to rescue bone marrow aplasia following high-dose chemotherapy for solid tumors or multiple myeloma. Recently, HSCs are also spotlighted in the field of regenerative medicine for the amelioration of symptoms caused by neurodegenerative diseases, heart diseases, and others. Although the demand for HSCs has been growing, their supply often fails to meet the demand of the patients needing transplant due to a lack of histocompatible donors or a limited cell number. This review focuses on the generation and large-scale expansion of HSCs, which might overcome current limitations in the application of HSCs for clinical use. Furthermore, current proof of concept to replenish hematological homeostasis from non-hematological origin will be covered.
Bone Marrow ; Cell Count ; Drug Therapy ; Heart Diseases ; Hematologic Diseases ; Hematologic Neoplasms ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells* ; Homeostasis ; Humans ; Metabolism, Inborn Errors ; Multiple Myeloma ; Neurodegenerative Diseases ; Regenerative Medicine ; Stem Cells ; Tissue Donors

Umbilical cord blood (CB) has been an alternative hematopoietic stem cell source especially for patients without an appropriate marrow or mobilized peripheral blood donor. Although many studies have shown similar overall survival rates after CB transplantation compared with other donor sources, higher rate of non-relapse mortality is a major obstacle for a successful CB transplantation. Thus, selecting a best appropriate unit is very important to improve the outcome of CB transplantation. Adequate cell dose and better HLA matching (antigen-level for -A, -B, and allele-level for -DRB1) have been considered most important criteria of donor choice for CB transplantation. In recent, other criteria including non-inherited maternal antigens, HLA-C matching, allele-level matching at 8 loci (-A, -B, -C, -DRB1), and anti-HLA antibodies are also suggested as factors that might affect the outcome of CB transplantation. This review will highlight current issues regarding criteria of donor choice for CB transplantation. Finally, I will introduce the algorithm and detailed guideline for CB selection recently developed in Korea, which may help physicians to choose best unit available.
Antibodies ; Blood Donors ; Bone Marrow ; Fetal Blood* ; Hematopoietic Stem Cell Transplantation* ; Hematopoietic Stem Cells* ; HLA-C Antigens ; Humans ; Korea ; Mortality ; Survival Rate ; Tissue Donors

BACKGROUND: Wilms tumor, the most common primary malignant renal tumor of childhood, has relatively good prognosis among solid tumors occurring in childhood because of the improved operation skill, proper selection of chemotherapeutic agents, and combined radiotherapy on the primary and distant metastatic sites after nephrectomy. However, successful therapy has been associated with long-term toxicity occurring years or decades later. So it is important to identify and understand the possible late effects of treatment for Wilms tumor. METHODS: We reviewed 73 cases of Wilms tumor who were diagnosed and treated from Mar., 1983 to Nov., 1996 and calculated the survival rate. In addition, 42 cases were investigated to see the late effects of treatment for Wilms tumor since Feb., 1993, especially with predesigned indices such as blood pressure, blood urea nitrogen(BUN), serum creatinine(S-Cr), 24 hour urine protein/creatinine(24 HU Pr/Cr), 24 hour urine microalbumin(24 HU MA), 24 hour urine beta2-microglobulin/creatinine(24 HU beta2-MG/Cr). RESULTS: Overall survival rate of Wilms tumor was 86% in 5 years. There was significant difference in survival between stage I, II, III group and stage IV, V group(90% vs 72%, P=0.032), and survival rate of favorable histology group was higher than that of unfavorable histology group(92% vs 73%, P=0.043). Of the 42 cases in our study of late effects, no patient has presented significant late sequelae causing morbidity, and there were one case of transient hypertension, three cases of microalbuminuria, three cases of proteinuria, one case of asymptomatic microscopic hematuria, one case of radiation hepatitis and two cases of nut-cracker syndrome. No abnormality was noted in BUN, S-Cr, or 24 HU beta2-MG/Cr. CONCLUSION: Wilms tumor in our center have an excellent prognosis and no significant late sequelae that might affect long-term morbidity were found. But thorough and further longer follow-up is mandatory to understand the possible late effects fully, so that cope with properly and improve the quality of life.
Blood Pressure ; Follow-Up Studies ; Hematuria ; Hepatitis ; Humans ; Hypertension ; Nephrectomy ; Prognosis ; Proteinuria ; Quality of Life ; Radiotherapy ; Survival Rate* ; Urea ; Wilms Tumor*

In the initial published version of this article, there was a mistake in the title. The correct title should be “Impact of Day 14 Peripheral Blood Chimerism after Allogeneic Hematopoietic Stem Cell Transplantation on the Treatment Outcome of Non-Malignant Disease”.

PURPOSE: This study was performed to compare the clinical characteristics of 2009 pandemic influenza A(H1N1) [A(H1N1) pdm09] and seasonal influenza A infection in the pediatric cancer patients. METHODS: A retrospective review was performed in the pediatric cancer patients who had confirmed A(H1N1)pdm09 infection at Samsung Medical Center from August 2009 to February 2010. For the comparison, the medical records of pediatric cancer patients with seasonal influenza A from January 2000 to May 2009 were reviewed retrospectively. RESULTS: Eighty-two A(H1N1)pdm09 infections were confirmed in the pediatric cancer patients. Ten patients (12.2%) developed complicated clinical course by lower respiratory infections or extrapulmonary infections; 4 pneumonia, 1 bronchitis, 1 pericarditis with pneumonia, 1 encephalitis with pneumonia, 2 meningitis and 1 pericarditis. Three patients received mechanical ventilator and ICU care. Three pediatric cancer patients (3.7%) died. The risk factors related to complicated A(H1N1)pdm09 infections were date of infection (44-45th week 2009) and nosocomial infection. When comparing with previous seasonal influenza A infections, more prompt and aggressive antiviral therapy was given in A(H1N1)pdm09 infections. CONCLUSION: The A(H1N1)pdm09 infections caused a various clinical manifestations including fatal cases in pediatric cancer patient during pandemic season. There was no significant difference in clinical course between influenza A(H1N1)pdm09 and seasonal influenza A infections except the antiviral treatment strategy.
Bronchitis ; Child ; Cross Infection ; Encephalitis ; Humans ; Influenza, Human ; Medical Records ; Meningitis ; Pandemics ; Pericarditis ; Pneumonia ; Respiratory Tract Infections ; Retrospective Studies ; Risk Factors ; Seasons ; Ventilators, Mechanical

Purpose: Children with Down syndrome (DS) show a higher risk of acute leukemia than those without DS. In this study, we investigated the nationwide incidence of acute leukemia among children with DS and compared their epidemiologic characteristics with those of children with acute leukemia but without DS. Materials and Methods: Using the National Health Insurance Service database, we selected patients with acute leukemia aged 0–19 years at diagnosis between 2007 and 2016. Results: Among the 4,697 children with acute leukemia, 54 (1.1%) had DS. The median incidence rate of leukemia with DS by year was 1.3% (range, 0.2%–2.0%). Sixteen patients with acute lymphoblastic leukemia (ALL; 29.6%) and 36 with acute myeloid leukemia (AML; 66.7%) had DS. The DS group showed younger age at diagnosis than the non-DS group, and diagnosis of AML was more frequent in the DS group than in the non-DS group (3 years vs. 9 years, p<0.001; 66.7% vs. 32.4%, P<0.001, respectively). The 5-year overall survival was comparable between the DS and non-DS groups (88.0% vs. 81.9%, p=0.375). Among all the Koreans born between 2007 and 2008, the incidences of acute leukemia, ALL, and AML were 49.25, 20.75, and 163.38 times higher, respectively, in the DS group than in the non-DS group. Conclusion Our findings support the fact that the incidence of acute leukemia is higher among patients with DS than among those without DS in Korea. However, the DS and non-DS groups in this study had a comparable overall survival rate.

PURPOSE: As increased level of prostaglandin has been identified in the bony lesions of Langerhans cell histiocytosis (LCH), we speculated that indomethacin, a potent prostaglandin inhibitor, may be effective for patients with LCH. METHODS: Retrospective review of 8 children with LCH (male 7, female 1) treated with indomethacin at Seoul National University Children's Hospital from September 1999 to February 2001 was done. The dose of indomethacin ranged from 1.8 to 2.8 mg/kg/day in two divided doses. RESULTS: Four patients with single bony lesion had a complete response to treatment. Among them one patient was treated with indomethacin after fourth relapse. Two patients with multiple bony lesions seemed to have partial response to treatment with indomethacin initially but showed disease progression later. Two patients with extraosseous lesion did not respond, but skull lesions were resolved after treatment. No serious toxicities of indomethacin treatment were observed. CONCLUSION: Indomethacin seems to be a very convenient and useful therapy for LCH involving single bony lesion. The mechanism how the LCH imporves in response to indomethacin has to be elucidated. Whether it has a specific role in slowing disease progression or we are seeing merely a spontaneous remission has to be studied in large scale.
Child ; Disease Progression ; Female ; Histiocytosis, Langerhans-Cell* ; Humans ; Indomethacin* ; Prostaglandin Antagonists ; Recurrence ; Remission, Spontaneous ; Retrospective Studies ; Seoul ; Skull

PURPOSE: Recently Wilms tumor gene (WT1) transcripts have been detected in leukemia regardless of the disease subtype and the specific DNA markers suggesting that WT1 gene might be a useful panleukemic marker for monitoring minimal residual disease (MRD). This study was performed to investigate the expression of WT1 gene by a quantitative methods and to find the prognostic value of WT1 gene in childhood acute leukemia. METHODS: From the mononuclear cells isolated from bone marrow aspirates and peripheral bloods of 22 childhood acute and chronic leukemia patients, mRNA were extracted for the reverse transcriptase-polymerase chain reactions (RT-PCR). Relative levels of WT1 gene expression was calculated by using the value in K562 cell line to be 1.00 as a positive control. RESULTS: The sensitivity of detection of MRD with WT1 primers was 10 4 and comparable to that of bcr/abl expression in K562 cells and a patient with CML in blast crisis. WT1 gene expression was detected in 17 of 22 (77%) patients; 9/10 of acute lymphoblastic leukemia (ALL), 6/10 acute myelogenous leukemia (AML), 1 acute mixed lineage leukemia (AMLL) and 1 chronic myelogenous leukemia (CML) in blast crisis. In 4 AML patients who received autologous peripheral blood stem cell transplantation (PBSCT), two patients relapsed after reappearance of WT1 gene expression in bone marrow aspirates and the remaining two were in complete remission without expression of WT1 gene. CONCLUSION: These results show that WT1 gene expression is frequently noted in childhood acute leukemia and can be a useful sensitive marker for the detection of MRD comparable to bcr/abl transcripts. WT1 gene can be used as a panleukemic marker for the MRD monitoring for the evaluation of the remission status and in predicting early relapse in children with acute leukemia in the molecular levels. It may also be a useful tool for the detection of leukemic cell contamination in the process of peripheral blood stem cell transplantation.
Blast Crisis ; Bone Marrow ; Cell Line ; Child ; Gene Expression ; Genetic Markers ; Humans ; K562 Cells ; Leukemia* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Leukemia, Myeloid, Acute ; Neoplasm, Residual ; Peripheral Blood Stem Cell Transplantation ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Recurrence ; RNA, Messenger ; Wilms Tumor

PURPOSE: Retrospective study was performed to evaluate the survivals, remission rate and complications of induction chemotherapy using N(4)-behenoyl-1-beta-D-arabinofuranosylcytosine (BH-AC), idarubicin and 6-thioguanine (6-TG) in newly diagnosed childhood acute myelogenous leukemia. METHODS: From July 1994 to March 2000, 40 children (male 30, female 10) were enrolled in the study. From day 0 to 6 of induction, BH-AC 300 mg/m(2)/day was administered intravenously over 3 hours and from day 7 to 9, dosage was adjusted according to residual leukemic blasts in day 7 bone marrow aspirates. Idarubicin 10 mg/m(2)/day was administered intravenously over 15 minutes from day 0 to 2 and 6-TG 100 mg/m(2)/ day orally divided in two from day 0 to 6. Median age at diagnosis was 4.4 years (1 month~14.9 years) with a distribution according to the FAB classification of 1 M1, 10 M2, 13 M4, 5 M4E, 7 M5a, 3 M6 and 1 M7. RESULTS: Complete remission (CR) rate was 82.5% (33/40) with one cycle of induction chemotherapy and 90.0% (36/40) with additional cycle (BH-AC and idarubicin). One patient achieved partial remission with one cycle and was lost to follow-up, and 3 died of septic shock with disseminated intravascular coagulopathy during induction. Median time to CR from diagnosis was 28 days (25~68) and recovery from neutropenia (ANC> 1,000/muL) was achieved on median day 24 (21~44). All 40 patients had a fever during neutropenic period. Toxicities such as diarrhea, mucositis, nausea and vomiting were observed over half of the patients but tolerable and transient. Five-year overall, relapse- free and event-free survivals were 54.0%, 51.1% and 46.7%, respectively. CONCLUSION: These data show that this regimen is superior to others with high remission rate and well tolerated.
Bone Marrow ; Child ; Classification ; Diagnosis ; Diarrhea ; Disease-Free Survival ; Female ; Fever ; Humans ; Idarubicin* ; Induction Chemotherapy* ; Leukemia, Myeloid, Acute* ; Lost to Follow-Up ; Mucositis ; Nausea ; Neutropenia ; Retrospective Studies ; Shock, Septic ; Thioguanine* ; Vomiting

BACKGROUND: The impact of early peripheral blood chimerism on the outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is unclear. We aimed to determine whether day 14 peripheral blood chimerism after allo-HSCT predicts outcomes in patients with non-malignant diseases. METHODS: Data from 56 patients who received allo-HSCT between April 2007 and March 2016 were retrospectively analyzed. Chimerism was evaluated using short-tandem repeat polymerase chain reaction, with mixed chimerism (MC) defined as greater than 1% recipient cells which was further categorized into low-level MC (> 1% and < 15% of recipient-derived cells) and high-level MC (≥ 15% of the recipient-derived cells). RESULTS: Thirty-six patients showed complete donor chimerism (CC), 14 low-level MC, and 6 high-level MC at day 14 post-transplant. The estimated 5-year event-free survival (EFS) was higher in the CC or low-level MC groups than in the high-level MC group (86.1% vs. 71.4% vs. 33.3%; P = 0.001). In BM or peripheral blood stem cell (BM/PBSC) transplants, the 5-year EFS was higher in the CC or low-level MC group than in the high-level MC group (93.1% vs. 66.7% vs. 0%; P < 0.001). However, in cord blood transplants, the 5-year OS and EFS according to the day 14 peripheral blood chimerism did not reach statistical significance. CONCLUSION: Although CC is not always necessary after allo-HSCT for non-malignant diseases, our data suggest that day 14 peripheral blood chimerism may predict outcomes in patients with non-malignant diseases who underwent BM/PBSC transplants.
Bone Transplantation ; Chimerism ; Disease-Free Survival ; Fetal Blood ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Humans ; Polymerase Chain Reaction ; Retrospective Studies ; Stem Cells ; Tissue Donors ; Treatment Outcome